A long-range goal of this laboratory is to detail the events that occur during the initiation of transcription of class II genes. Our intent is to formulate an understanding of the revelant mechanisms that operate in the regulation of expression of class II genes. This will be accomplished by characterization of the proteins involved and their various protein: DNA and protein:protein interactions. To this end, the overall aim of this proposal is to continue and expand studies now in progress in my laboratory on a novel protein factor, Dr, that interacts with a key component of the RNA polymerase II transcription machinery, the TATA binding protein. This protein:protein interaction results in repression of class II gene expression. Regulation of gene expression is a complex process that can be achieved at multiple steps. Studies have demonstrated that initiation of transcription is a primary site for regulation. The first step during formation of a transcription competent complex is the binding the TFIID to the TATA motif, providing a recognition site for the association of RNA polymerase II and auxiliary proteins. TFIID also interacts with activator proteins. A great deal of effort has been directed towards the isolation of proteins that activate transcription. However, an equally important mechanism for regulating gene expression is repression. Studies carried out during the past years have uncovered a mechanism for repression involving protein:protein interactions.